Fluorescently Labeled Gadolinium Ferrate/Trigadolinium Pentairon(III) Oxide Nanoparticles: Synthesis, Characterization, In Vivo Biodistribution, and Application for Visualization of Myocardial Ischemia-Reperfusion Injury.

Various gadolinium compounds have been proposed as contrasting agents for magnetic resonance imaging (MRI). In this study, we suggested a new synthesis method of gadolinium ferrate/trigadolinium pentairon(III) oxide nanoparticles (GF/TPO NPs). The specific surface area of gadolinium ferrate (GdFeO3) and trigadolinium pentairon(III) oxide (Gd3Fe5O12) nanoparticles was equal to 42 and 66 m2/g, respectively. The X-ray diffraction analysis confirmed that the synthesized substances were GdFeO3 and Gd3Fe5O12. The gadolinium content in the samples was close to the theoretically calculated value. The free gadolinium content was negligible. Biodistribution of the GF/TPO NPs was studied in rats by fluorescent imaging and Fe2+/Fe3+ quantification demonstrating predominant accumulation in such organs as lung, kidney, and liver. We showed in the in vivo rat model of myocardial ischemia-reperfusion injury that GF/TPO NPs are able to target the area of myocardial infarction as evidenced by the significantly greater level of fluorescence. In perspective, the use of fluorescently labeled GF/TPO NPs in multimodal imaging may provide basis for high-resolution 3D reconstruction of the infarcted heart, thereby serving as unique theranostic platform.

Theranostic Platforms Based on Silica and Magnetic Nanoparticles Containing Quinacrine, Chitosan, Fluorophores, and Quantum Dots.

In this paper, we describe the synthesis of multilayer nanoparticles as a platform for the diagnosis and treatment of ischemic injuries. The platform is based on magnetite (MNP) and silica (SNP) nanoparticles, while quinacrine is used as an anti-ischemic agent. The synthesis includes the surface modification of nanoparticles with (3-glycidyloxypropyl)trimethoxysilane (GPMS), the immobilization of quinacrine, and the formation of a chitosan coating, which is used to fix the fluorophore indocyanine green (ICG) and colloidal quantum dots AgInS2/ZnS (CQDs), which serve as secondary radiation sources. The potential theranostic platform was studied in laboratory animals.

Terahertz high-resolution spectroscopy of thermal decomposition gas products of diabetic and non-diabetic blood plasma and kidney tissue pellets.

SIGNIFICANCE: One of the modern trends in medical diagnostics is based on metabolomics, an approach allowing determination of metabolites which can be the specific features of disease. High-resolution gas spectroscopy allows investigation of the gas metabolite content of samples of biological origin. We present the elaboration of a method of studying diabetic and non-diabetic biological samples, prepared as pellets, by terahertz (THz) high-resolution spectroscopy. AIM: The main idea of the work is studying the content of thermal decomposition gas products of diabetic and non-diabetic dried blood plasma and kidney tissues for revealing the set of gas-markers that characterized the diabetes by the THz high-resolution spectroscopy method. APPROACH: We present an approach to study the diabetic and non-diabetic blood plasma (human and rats) and kidney tissues (rats), using high-resolution spectroscopy based on the non-stationary effect of THz frequency range. The methods of preparing the blood and kidney tissue samples as pellets and of vaporizing the samples were developed. RESULTS: The measurements of rotational absorption spectra of vapors at heating the pellets prepared from blood and kidney tissue were carried out in 118 to 178 GHz frequency range. The absorption lines appearing in spectra of the sample vapors were detected and identified. The molecular contents of thermal decomposition products differed for non-diabetic and diabetic samples; e.g., main marker is acetone appearing in the diabetic blood (human and rats) and in the diabetic kidney tissue. CONCLUSIONS: Our paper illustrates the potential ability for determining the metabolite content of biological samples for diagnostics and prognosis of diseases for clinical medicine.

Terahertz spectroscopy of diabetic and non-diabetic human blood plasma pellets.

SIGNIFICANCE: The creation of fundamentally new approaches to storing various biomaterial and estimation parameters, without irreversible loss of any biomaterial, is a pressing challenge in clinical practice. We present a technology for studying samples of diabetic and non-diabetic human blood plasma in the terahertz (THz) frequency range. AIM: The main idea of our study is to propose a method for diagnosis and storing the samples of diabetic and non-diabetic human blood plasma and to study these samples in the THz frequency range. APPROACH: Venous blood from patients with type 2 diabetes mellitus and conditionally healthy participants was collected. To limit the impact of water in the THz spectra, lyophilization of liquid samples and their pressing into a pellet were performed. These pellets were analyzed using THz time-domain spectroscopy. The differentiation between the THz spectral data was conducted using multivariate statistics to classify non-diabetic and diabetic groups' spectra. RESULTS: We present the density-normalized absorption and refractive index for diabetic and non-diabetic pellets in the range 0.2 to 1.4 THz. Over the entire THz frequency range, the normalized index of refraction of diabetes pellets exceeds this indicator of non-diabetic pellet on average by 9% to 12%. The non-diabetic and diabetic groups of the THz spectra are spatially separated in the principal component space. CONCLUSION: We illustrate the potential ability in clinical medicine to construct a predictive rule by supervised learning algorithms after collecting enough experimental data.

In vitro toxicity of FemOn, FemOn-SiO2 composite, and SiO2-FemOn core-shell magnetic nanoparticles.

Over the last decade, magnetic iron oxide nanoparticles (IONPs) have drawn much attention for their potential biomedical applications. However, serious in vitro and in vivo safety concerns continue to exist. In this study, the effects of uncoated, FemOn-SiO2 composite flake-like, and SiO2-FemOn core-shell IONPs on cell viability, function, and morphology were tested 48 h postincubation in human umbilical vein endothelial cell culture. Cell viability and apoptosis/necrosis rate were determined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and annexin V-phycoerythrin kit, respectively. Cell morphology was evaluated using bright-field microscopy and forward and lateral light scattering profiles obtained with flow cytometry analysis. All tested IONP types were used at three different doses, that is, 0.7, 7.0, and 70.0 µg. Dose-dependent changes in cell morphology, viability, and apoptosis rate were shown. At higher doses, all types of IONPs caused formation of binucleated cells suggesting impaired cytokinesis. FemOn-SiO2 composite flake-like and SiO2-FemOn core-shell IONPs were characterized by similar profile of cytotoxicity, whereas bare IONPs were shown to be less toxic. The presence of either silica core or silica nanoflakes in composite IONPs can promote cytotoxic effects.

Silicon-containing nanocarriers for targeted drug delivery: synthesis, physicochemical properties and acute toxicity.

Silicon-containing nanoparticles (NPs) are considered promising drug carriers for targeted drug delivery. In this study, we investigated the physical and chemical properties of silicon-containing NPs, including silica and organomodified silica NPs (SiO2NPs and OrSiO2NPs, respectively), with different surface modifications, with the aim of increasing drug-loading efficiency. In addition, we described the original synthesis methods of different sizes of OrSiO2NPs, as well as new hybrid OrSiO2NPs with a silica core (SiO2 + OrSiO2NPs). Animal experiments revealed that the silicon-containing NPs investigated were non-toxic, as evidenced by a lack of hemodynamic response after intravenous administration. Bioelimination studies showed rapid renal excretion of OrSiO2NPs. In drug release kinetics studies, adenosine was immobilized on SiO2NPs using three different approaches: physical adsorption, ionic, and covalent bonding. We observed that the rate of adenosine desorption critically depended on the type of immobilization; therefore, adenosine release kinetics can be adjusted by SiO2NP surface modification technique. Adsorption of adenosine on SiO2 + OrSiO2NPs resulted in a significant attenuation of adenosine-induced hypotension and bradycardia.

Targeted drug delivery into reversibly injured myocardium with silica nanoparticles: surface functionalization, natural biodistribution, and acute toxicity.

The clinical outcome of patients with ischemic heart disease can be significantly improved with the implementation of targeted drug delivery into the ischemic myocardium. In this paper, we present our original findings relevant to the problem of therapeutic heart targeting with use of nanoparticles. Experimental approaches included fabrication of carbon and silica nanoparticles, their characterization and surface modification. The acute hemodynamic effects of nanoparticle formulation as well as nanoparticle biodistribution were studied in male Wistar rats. Carbon and silica nanoparticles are nontoxic materials that can be used as carriers for heart-targeted drug delivery. Concepts of passive and active targeting can be applied to the development of targeted drug delivery to the ischemic myocardial cells. Provided that ischemic heart-targeted drug delivery can be proved to be safe and efficient, the results of this research may contribute to the development of new technologies in the pharmaceutical industry.